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B7-H1 agonists suppress the PI3K/AKT/mtor pathway by degrading p110γ and independently induce cell death.
Chen, Ling; Hou, Ping; Zou, Yu-Lian; Wang, Yang; Zhou, Lin-Lin; Hu, Li; Hu, Yan; Zhang, Qiu-Yu; Huang, Li-Ping; Lin, Lin.
Afiliación
  • Chen L; Institute of Immunotherapy, Fujian Medical University, Fuzhou, Fujian, 350102, China. Electronic address: chenl337@fjmu.edu.cn.
  • Hou P; Institute of Immunotherapy, Fujian Medical University, Fuzhou, Fujian, 350102, China.
  • Zou YL; Institute of Immunotherapy, Fujian Medical University, Fuzhou, Fujian, 350102, China.
  • Wang Y; Institute of Immunotherapy, Fujian Medical University, Fuzhou, Fujian, 350102, China.
  • Zhou LL; Institute of Immunotherapy, Fujian Medical University, Fuzhou, Fujian, 350102, China.
  • Hu L; Institute of Immunotherapy, Fujian Medical University, Fuzhou, Fujian, 350102, China.
  • Hu Y; Public Technology Service Center, Fujian Medical University, Fuzhou, Fujian, 350102, China.
  • Zhang QY; Institute of Immunotherapy, Fujian Medical University, Fuzhou, Fujian, 350102, China; Department of Immunology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, 350102, China.
  • Huang LP; Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, Fujian, China.
  • Lin L; Department of Obstetrics, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, Fujian, China.
Cancer Lett ; 584: 216615, 2024 Mar 01.
Article en En | MEDLINE | ID: mdl-38199586
ABSTRACT
The biological role of B7-H1 intrinsic signal is reportedly diverse and controversial, its signal pathway remains unclear. Although B7-H1 blocking antibodies were found to have agonist capacity, their binding features and agonist mechanisms need further investigation. Here, by constructing cell strains with full-length or truncated B7-H1, we found that B7-H1 functioned as a receptor to transmit cell death signal from PD-1 protein or anti-B7-H1s through its cytoplasmic domain. Specific binding to the IgV-like domain of B7-H1 was required for the downstream signal. Upon agonists interaction, B7-H1 regulated the degradation of phosphoinositide 3-kinases (PI3Ks) subunit p110γ, subsequently inhibited the PI3K/AKT/mTOR pathway, and significantly increased autophagy. Moreover, B7-H1 agonists also suppressed ubiquitylation in B7-H1+cells by reducing ubiquitin-activating enzyme (E1), eventually leading to cell death. Finally, we validated the receptor role of B7-H1 in multiple tumor cells and demonstrated that B7-H1 agonists could suppress tumor progression independent of T cells in vivo. Our findings revealed that B7-H1 agonists functions as a PI3K inhibitor and may offer new strategies for PI3K targeting therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt Idioma: En Revista: Cancer Lett Año: 2024 Tipo del documento: Article Pais de publicación: Irlanda
Texto completo
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Imprimir
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fosfatidilinositol 3-Quinasas / Proteínas Proto-Oncogénicas c-akt Idioma: En Revista: Cancer Lett Año: 2024 Tipo del documento: Article Pais de publicación: Irlanda